This is a proposal to the National Institutes of Health to establish a Bioengineering Research Partnership to develop a spectroscopic imaging methodology for diagnosing pre-invasive neoplasia (dysplasia) and monitoring its progression. The proposed program is based on optical spectroscopic clinical instrumentation and associated diagnostic algorithms successfully developed at the MIT Spectroscopy Laboratory. The instrument to be developed will have two components, a system for wide-area imaging of neoplasia, based on light scattering spectroscopy i(LSS), and an optical fiber probe device for studying suspect regions thus revealed, based on tri-modal spectroscopy i(TMS). The goal of the program is to develop and perfect the new technology and assess its application to the diagnosis, characterization, and therapy of neoplastic progression in human patients in real time, The detection and monitoring of neoplastic lesions in the oral cavity and the cervix will be used as model systems for establishing the potential of the technology. In addition, basic studies to further improve the technology and its ability to characterize pre-invasive neoplasia will be conducted. Six projects will be undertaken, each led by an experienced investigator: (I) Prototype instruments and diagnostic algorithms for clinical studies will be developed, maintained and perfected. Clinical studies will be conducted on patients with suspected lesions in the (2) oral cavity and (3) uterine cervix to evaluate and perfect the technology for diagnosing and monitoring dysplasia and predicting the patient's response to chemopreventive and immunotherapeutic agents. Two basic projects aimed at enhancing the diagnostic accuracy of the clinical instrumentation will be undertaken, one (4) to explore the use of quasi-multiple scattered light to enhance the sensitivity and provide depth resolution to LSS imaging, and a second (5) to develop novel spectroscopic end-points based on well-characterized molecular and cellular events associated with the progression and regression of disease. (6) Pathology support activities will include analysis of oral and cervical tissues for molecular markers, and analysis of histologic sections of the same biopsy tissue by computer-assisted quantitative image analysis. An administrative core will coordinate the multidisciplinary activities of the program and insure information sharing and efficient communication. The partnership, composed of expert investigators at six institutions, will include experienced bioengineers with training in physics and mechanical/electrical engineering, pathologists experienced in cancer research, and hospital-based clinicians specializing in oral and cervical dysplasia.